We propose to investigate the molecular basis of mutagenesis. Bacteriophage T4, having normal and aberrant DNA polymerases (mutators and antimutators), will be used as a model system for study. Experiments, in vitro and in vivo, are designed to measure individual steps in the mutational pathway A:T yields G:C using the base analogue 2-aminopurine as a biochemical and genetic probe. A model for aminopurine induced mutagenesis is proposed. The model provides a general framework with which to analyze individual experimental results for the mispairing of aminopurine with thymine and cytosine and resulting transitions. These experimental results in concert with model based predictions should provide a clearer picture of how organisms edit errors which occur during DNA synthesis. Thus, in a general sense, this proposal is concerned with cellular mechanisms used to maintain genetic integrity through successive generations. The potential significance of the results might have broad application in the areas of carcinogenesis, aging, and evolution.